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Injection therapy for subacute and chronic low-back pain

(Review)

Staal JB, de Bie R, de Vet HCW, Hildebrandt J, Nelemans P

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library

2011, Issue 2

http://www.thecochranelibrary.com

Injection therapy for subacute and chronic low-back pain (Review)

Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

http://www.thecochranelibrary.com

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

10DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

15CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

39DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 epidural corticosteroids versus placebo injections, Outcome 1 Percentage improved over 1 to 3

months. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

Analysis 1.2. Comparison 1 epidural corticosteroids versus placebo injections, Outcome 2 Percentage pain relief over 3 to 5

weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

Analysis 2.1. Comparison 2 epidural corticosteroid injections versus other treatments, Outcome 1 General improvement at

2 months. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

Analysis 3.1. Comparison 3 Facet joint injections with corticosteroids versus placebo injections, Outcome 1 Self-rated

improvement at 1 month. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

Analysis 3.2. Comparison 3 Facet joint injections with corticosteroids versus placebo injections, Outcome 2 Self rated

improvement at 6 months. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

Analysis 4.1. Comparison 4 Facet joint injections with corticosteroids versus other injections, Outcome 1 Improvement in

pain severity at 1 month. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Analysis 4.2. Comparison 4 Facet joint injections with corticosteroids versus other injections, Outcome 2 Improvement in

pain severity at 3 months. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Analysis 5.1. Comparison 5 Facet joint injections with local anaesthetics versus other injections, Outcome 1 Pain reduction

post-treatment in positive group (VAS) (facet joint assumed to be the primary source of pain). . . . . . . 44

Analysis 6.1. Comparison 6 Local injections with corticosteroids versus placebo injections, Outcome 1 Self-reported

improvement at 2 weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Analysis 6.2. Comparison 6 Local injections with corticosteroids versus placebo injections, Outcome 2 Self-reported

improvement posttreatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Analysis 7.1. Comparison 7 Local injections with anaesthetics versus placebo injections, Outcome 1 Pain intensity at 2

weeks (VAS). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Analysis 7.2. Comparison 7 Local injections with anaesthetics versus placebo injections, Outcome 2 Self-reported

improvement at 2 weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

46ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

48APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

49WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

49HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

50CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

50DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

51INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iInjection therapy for subacute and chronic low-back pain (Review)


[Intervention Review]


J Bart Staal1, Rob de Bie2, Henrica CW de Vet3, Jan Hildebrandt4, Patty Nelemans5

1Institute for Quality of Health Care (IQ health care), Radboud University Nijmegen Medical Center, Nijmegen, Netherlands.2Department of Epidemiology, Maastricht University, Maastricht, Netherlands. 3Department of Epidemiology and Biostatistics,

EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, Netherlands. 4University Medicine Goet-

tingen, Goettingen, Germany. 5Epidemiology, University of Maastricht, Maastricht, Netherlands

Contact address: J Bart Staal, Institute for Quality of Health Care (IQ health care), Radboud University Nijmegen Medical Center,

PO Box 9101, Nijmegen, 6500 HB, Netherlands. [email protected].

Editorial group: Cochrane Back Group.

Publication status and date: Edited (no change to conclusions), published in Issue 2, 2011.

Review content assessed as up-to-date: 29 March 2007.

Citation: Staal JB, de Bie R, de Vet HCW, Hildebrandt J, Nelemans P. Injection therapy for subacute and chronic low-back pain.

Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD001824. DOI: 10.1002/14651858.CD001824.pub3.


A B S T R A C T

Background

The effectiveness of injection therapy for low-back pain is still debatable. Heterogeneity of target tissue, pharmacological agent and

dosage generally found in randomized controlled trials (RCTs) points to the need for clinically valid comparisons in a literature synthesis.

Objectives

To determine if injection therapy is more effective than placebo or other treatments for patients with subacute or chronic low-back

pain.

Search methods

We updated the search of the earlier systematic review and searched the Cochrane Central Register of Controlled Trials, MEDLINE

and EMBASE databases from January 1999 to March 2007 for relevant trials reported in English, French, German, Dutch and Nordic

languages. We also screened references from trials identified.

Selection criteria

RCTs on the effects of injection therapy involving epidural, facet or local sites for subacute or chronic low-back pain were included.

Studies which compared the effects of intradiscal injections, prolotherapy or Ozone therapy with other treatments, were excluded unless

injection therapy with another pharmaceutical agent (no placebo treatment) was part of one of the treatment arms. Studies about

injections in sacroiliac joints and studies evaluating the effects of epidural steroids for radicular pain were also excluded.

Data collection and analysis

Two review authors independently assessed the quality of the trials. If study data were clinically and statistically too heterogeneous to

perform a meta-analysis, we used a best evidence synthesis to summarize the results. The evidence was classified into five levels (strong,

moderate, limited, conflicting or no evidence), taking into account the methodological quality of the studies.

1Injection therapy for subacute and chronic low-back pain (Review)


mailto:[email protected]

Main results

18 trials (1179 participants) were included in this updated review. The injection sites varied from epidural sites and facet joints (i.e.

intra-articular injections, peri-articular injections and nerve blocks) to local sites (i.e. tender- and trigger points). The drugs that were

studied consisted of corticosteroids, local anesthetics and a variety of other drugs. The methodological quality of the trials was limited

with 10 out of 18 trials rated as having a high methodological quality. Statistical pooling was not possible due to clinical heterogeneity

in the trials. Overall, the results indicated that there is no strong evidence for or against the use of any type of injection therapy.

Authors’ conclusions

There is insufficient evidence to support the use of injection therapy in subacute and chronic low-back pain. However, it cannot be

ruled out that specific subgroups of patients may respond to a specific type of injection therapy.

P L A I N L A N G U A G E S U M M A R Y


Injection therapy is one of many treatments available for patients with subacute (longer than six weeks) and chronic (longer than 12

weeks) low-back pain. Where the injection is given, what drug is used and why the injection is given can all vary.

The injection can be given into different parts of the spine (the space between the vertebrae, around the nerve roots, or into the disc),

ligaments, muscles or trigger points (spots in the muscles that when pressed firmly will produce pain). Drugs that reduce swelling

(corticosteroids, non-steroidal anti-inflammatory (NSAIDs)) and pain (morphine, anaesthetics) are used. Injection therapy can be used

for individuals with low-back pain with or without pain and other symptoms in the leg.

A number of electronic databases of healthcare articles were searched up to March 2007. This search identified 18 randomized controlled

trials (RCTs; 1179 participants) that looked at injections with a variety of drugs compared to a placebo drug or other drugs. The

injections were given into the epidural space (between the vertebrae of the back and outside the coverings that surround the spinal

cord), the facet joints (the joints of two vertebrae), or tender spots in the ligaments or muscles.

The review authors rated ten of the 18 RCTs as having a low risk of bias in the way the trials were conducted and reported. They

were unable to statistically pool the results because the injection sites, drugs used and outcomes measured were too varied. Only five of

the 18 trials reported significant results in favour of one of the treatment arms. The reviewer authors considered the likely treatment

benefits to be worth the potential harms in only two studies.

In nine out of the 18 studies, side effects such as headache, dizziness, transient local pain, tingling and numbness and nausea were

reported in small numbers of patients. The use of morphine was more frequently associated with itching, nausea and vomiting. Rare

but more serious complications of injection therapy have been mentioned in the literature, such as cauda equina syndrome, septic facet

joint arthritis, discitis, paraplegia, paraspinal abscesses. Although the absolute frequency of these complications may be rare, these risks

should be taken into consideration.

Based on these results, the review authors concluded that there is no strong evidence for or against the use of any type of injection

therapy for individuals with subacute or chronic low-back pain.

B A C K G R O U N D

Numerous treatments have been promoted as useful to reduce

the individual and socio-economic burden of low-back pain, but

many controversies still exist on the effectiveness of the available

treatment options (Weinstein 2004; Airaksinen 2006). Injection

therapy is one of the treatments for patients with subacute and

chronic low-back pain that needs careful evaluation with respect



to its effectiveness for short- and long-term pain relief. In order

to investigate the effects of injection therapy for low-back pain

in a systematic review, it should be realized that the content of

this treatment method, as studied in randomized controlled trials

(RCTs), may show a large degree of variation. The same holds for

daily clinical practice, which underlines the need to make clin-

ically valid comparisons of injection therapy interventions. The

first source of variation in the content of injection therapy is the

location of the injection and the tissue that is targeted for injec-

tion. The injection can be given into the facet joints, the epidu-

ral space, the spinal nerve root, the intervertebral disc, the lum-

bar sympathetic chain, sacro-iliac joints and also into local liga-

ments, muscles or trigger points (Airaksinen 2006). Second, the

pharmacological agent that is used for the injection varies from

different types of corticosteroids aimed at reducing inflammation

and anaesthetics aimed at pain relief, to a variety of other drugs,

all with potentially different dosages. Third, the indications for

the injection therapy may also be different. Injection therapy can

be applied in cases of acute, subacute or chronic low-back pain

with or without signs of nerve root compression. For obvious rea-

sons, the specific characteristics of the injection therapy with re-

spect to target tissue, pharmacological agent and dosage depends

on the presumed pathophysiological mechanisms leading to pain.

In some cases, injections are used for diagnostic purposes rather

than treatment. Injections into facet joints, for example, have been

presented as a diagnostic test for the so-called lumbar facet joint

syndrome (Mooney 1976; Mooney 1987). Furthermore, in some

RCTs, injection therapy is only one part of a multimodal treat-

ment package. These issues may challenge a valid assessment and

summation of the effects of injection therapy in patients with low-

back pain.

The present systematic review is an update of an earlier Cochrane

review on the effectiveness of injection therapy for subacute and

chronic low-back pain (Nelemans 2000). Many of the 21 studies

that were included in this prior systematic review were rated as

being of low methodological quality and in 11 of the 21 studies,

injection was compared with placebo. The authors concluded that

convincing evidence for the effectiveness of injection therapy was

still lacking and recommended large well-designed trials in this

field, preferably placebo-controlled (Nelemans 2000).

Since Nelemans 2000 et al was published, several new RCTs on

the effects of injections for low-back pain were published and the

method guidelines for systematic reviews in the field of low-back

pain were updated (van Tulder 2003). In order to reduce the clini-

cal heterogeneity identified in the earlier review, several more spe-

cific injection therapies have been covered in separate Cochrane

reviews. Therefore, the present systematic review does not include

the effects of intradiscal therapy (Niemisto 2003), prolotherapy

(i.e. injection of sclerosants) (Dagenais 2007) or epidural steroids

for radiculopathy due to disc herniation (registered as a title for

an upcoming Cochrane review). Although some overlap cannot

always be prevented since radiculopathy is not an exclusive diag-

nosis, we aim to exclude studies dealing specifically with epidu-

ral steroids for this particular study population from the present

update. Nelemans 2000 et al had included studies on epidural

steroids for radiculopathy in the earlier review. This update further

differs from the previous review with regard to the internal valid-

ity criteria that were used. We rated the studies according to the

eleven internal validity items recommended by van Tulder 2003

whereas Nelemans 2000 et al used a fifteen item list according to

ter Riet 1990 et al. In addition, we also added an assessment of

clinical relevance to the present review.

Because many studies in the review by Nelemans 2000 et al were

clinically heterogeneous, a major concern for the present update,

as stated before, was to come up with comparisons that made sense

from a clinical perspective. Therefore, we chose to classify studies

first according to the target tissue of the injection and second

according to the therapeutic agent that was used. If possible, these

strata were further subdivided into placebo-controlled trials and

those that compared injections with other treatments.

O B J E C T I V E S

The objective of this systematic review was to asses the effectiveness

of injection therapy for patients with subacute or chronic low-

back pain.

M E T H O D S

Criteria for considering studies for this review

Types of studies

Only RCTs were included. Non-randomized studies were ex-

cluded.

Types of participants

Patients aged from 18 to 70 years were included if they had low-

back pain with symptoms persisting for at least one month. Suba-

cute low-back pain was defined as lasting for four weeks or longer

and chronic as lasting for 12 weeks or longer.

Types of interventions

The treatment had to include injection therapy for pain relief.

The injection therapy was studied at three different injection sites:

facet joints, epidural sites, and local sites. Studies that compared

the effects of epidural steroids for radicular pain, intradiscal in-

jections, prolotherapy or Ozone therapy with other treatments



were excluded unless injection therapy with another pharmaceuti-

cal agent (no placebo treatment) was part of one of the treatment

arms. Studies about injections into sacroiliac joints and studies in

which the drugs were administered by means of a catheter and not

directly by means of an injection were also excluded.

Additional treatments were allowed.

Types of outcome measures

Pain was considered to be the most important outcome measure.

In order to be included for the present review, studies should at

least have incorporated this outcome measure. This could be ex-

pressed as the percentage of patients with pain relief or as mean

improvement on a continuous scale. Other important outcome

measures were: a global measure of improvement (e.g. overall im-

provement, proportion of patients recovered, subjective improve-

ment of symptoms), back-specific disability (expressed on a back-

specific index, such as the Roland Disability Questionnaire or the

Oswestry Disability Index), generic health status or well-being,

disability for work, and patient satisfaction (Bombardier 2000;

van Tulder 2003). These outcomes were evaluated on both a short-

term (less than six weeks) and long-term basis (longer than six

weeks). Side effects were also considered.

Search methods for identification of studies

RCTs published in English, French, German, Dutch and Nordic

languages were included. The literature searches carried out by

Nelemans et al were updated and reiterated in the same databases

for the period from 1999 to March 2007 (Nelemans 2000). MED-

LINE and EMBASE searches were based on the search strategies

recommended by the Cochrane Back Review Group (van Tulder

2003). The Cochrane CENTRAL database was also screened for

relevant RCTs. In addition, citation tracking of the studies re-

trieved by the search was performed until no new studies were

found. See Appendix 1 for the PubMed and EMBASE search

strategies.

Data collection and analysis

Study selection and data extraction

For the 2007 update, two authors (JBS, RdB) independently se-

lected new studies, assessed the methodological quality, and ex-

tracted the data (using a standardized form). This was conducted

in the same way, described in the following sections, as in the pre-

viously published systematic review (Nelemans 2000). A consen-

sus method was used to solve disagreements about the selection

of RCTs, and a third author (PN) was consulted if disagreement

persisted. First, the two authors screened the titles, abstracts and

keywords of all references identified by the literature search to de-

termine if they met the inclusion criteria. Second, the full text of

the article was retrieved for studies for which it was unclear from

the screening procedure whether or not the study had to be in-

cluded.

Methodological quality assessment

The methodological quality of the RCTs was independently as-

sessed by two authors (JBS, RdB), using the methodological cri-

teria recommended by the Cochrane Back Review Group (van

Tulder 2003). A consensus method was used to resolve disagree-

ments and a third author was consulted if disagreements persisted

(PN). The items were scored as either positive (+), negative (-)

or unclear (?). The criteria used, and their operationalization are

listed in Table 1.

Clinical relevance

Two authors (JBS and RdB) independently assessed the clinical

relevance of the included studies according to several questions

which were recommended by the Cochrane Back Review Group

(van Tulder 2003). Each question was scored positive (+) if the

clinical relevance item was met, negative (-) if the item was not met

and unclear (?) if data were not available to answer the question.

We considered a 20% improvement in pain scores (Salaffi 2004)

and a 10% improvement in functioning outcomes (Bombardier

2000) to be clinically important. See Table 2 for the questions

used.

Analysis

The results of each RCT were plotted as point estimates with cor-

responding 95% confidence intervals (95% CI) as far as possi-

ble. The clinical homogeneity was evaluated by exploring the dif-

ferences between the RCTs, taking into consideration the study

population, the injection sites, the content of the injection ther-

apy with regard to medication and dosage, reference treatments,

timing of follow-up measurements and measurement instruments.

Furthermore, a distinction was made between studies that com-

pared injection with a placebo injection and studies that compared

two or more active agents (Nelemans 2000). Attempts were made

to statistically pool the data of homogeneous studies for the out-

come measures pain, overall improvement and disability for short

and long-term follow-up. If subgroups of studies were considered

to be clinically homogeneous, the statistical homogeneity was for-

mally tested. If studies were considered clinically heterogeneous

and/or studies did not report their results in a way that enabled us

to perform statistical pooling (for example, for continuous data,

means were presented but no standard deviations) we refrained

from following a formal meta-analytic approach. In stead of this,

we summarized the results according to a rating system with five

levels of evidence (best evidence synthesis), based on the quality



and the outcome of the studies (van Tulder 2003). The following

levels of evidence were distinguished:

• Strong evidence - Consistent findings among multiple

high quality RCTs;

• Moderate evidence - Consistent findings among multiple

low quality RCTs or one high quality RCT;

• Limited evidence - one low quality RCT;

• Conflicting evidence - inconsistent findings among

multiple trials;

• No evidence - no RCTs.

High quality studies were defined as RCT which fulfilled six or

more of the internal validity criteria. The results were considered

to be consistent if 75% of the studies showed results in the same

direction.

R E S U L T S

Description of studies

See: Characteristics of included studies; Characteristics of excluded

studies.

Study selection

The original 1998 search yielded 40 relevant papers (Nelemans

2000). After detailed reading, 19 studies were excluded because

they included acute patients (pain for less than one month), they

did not describe the duration of the reported symptoms, they ap-

peared to be non-randomized or the anesthetic agent was injected

into the wound during surgery (Nelemans 2000). From the re-

maining 19 studies that were covered by Nelemans 2000 et al,

nine studies were excluded from the present update due to the

modified inclusion criteria. As stated earlier, studies on the effects

of corticosteroids for radiculopathy will be summarized in an-

other Cochrane review. This means that four studies which inves-

tigated the effects of corticosteroids in patients with radiculopathy

in comparison with a placebo injection (Cuckler 1985; Mathews

1987; Bush 1991; Rogers 1992) were excluded. Furthermore, one

study dealt with intradiscal injection (Simmons 1992), one study

dealt with prolotherapy (Ongley 1987), both of which are covered

in another Cochrane review, and another study included patients

who had cervical symptoms and did not present separate results

for the lower back (Hameroff 1981). Two studies were excluded

because the drugs were administered by means of a catheter (Dallas

1987; Glynn 1988) and not directly by means of an injection. In

addition, the study population of one of them consisted of patients

with chronic pain with only a small subgroup of patients labeled

as having low-back pain (Glynn 1988). Consequently, from the

previous search by Nelemans 2000 et al, only 10 studies were in-

corporated into the present update.

The March 2007 literature search update resulted in the identifica-

tion of 11 new references from MEDLINE, eight references from

EMBASE and one reference from additional reference checking.

Four references were included in both the MEDLINE and EM-

BASE search results, leaving 16 references potentially relevant for

the purpose of the review. After careful reading of the papers, the

two reviewers (JBS and RdB) decided that eight studies had to

be excluded. Two of them compared two different needling tech-

niques (Stojanovic 2005) or injection sites (Pneumaticos 2006).

One study compared radiofrequency denervation with an injec-

tion of a small amount of lidocaine which was considered a sham

treatment (Oh 2004). Other studies dealt with patients with

radiculopathy (sciatic nerve pain) (Bonetti 2005), with acute pa-

tients (Tuzun 2003), patients with osteoporosis (Ofluoglu 2007),

or made use of epidural catheterization (Fredman 1999). One

study appeared not to be a RCT (Ney 2006). Together with 10

studies from the earlier review, we ended up with 18 studies that

were considered relevant for the purpose of this review.

Characteristics of included studies

The number of participants in the included studies varied from 16

to 206 patients. Only three studies included more than 100 partic-

ipants (Lilius 1990; Carette 1991; Aldrete 2003). The study popu-

lation in most of the included studies consisted of patients who had

low-back pain with or without sciatica. Two studies dealt only with

post-laminectomy patients (Rocco 1989; Aldrete 2003) and in one

of these studies, some of the patients also had radicular symptoms

(Aldrete 2003). In two other studies, populations were mixed: pa-

tients were included with low-back pain and/or sciatica whether

or not combined with neurological signs (Beliveau 1971; Mauro

2000). In some studies, participation was limited to patients who

responded positively to a facet block with an anesthetic (Carette

1991; Manchikanti 2001) or to patients with radiologically con-

firmed facet joint osteoarthritis (Fuchs 2005). The injection sites of

the studies included can be subdivided into epidural sites (Beliveau

1971; Breivik 1976; Rocco 1989; Serrao 1992; Aldrete 2003;

Lierz 2004; Takada 2005), facet joints (Lilius 1990; Carette 1991;

Marks 1992; Revel 1999; Mayer 2004; Fuchs 2005) and local sites

(Sonne 1985; Garvey 1989; Collee 1991; Mauro 2000). Facet in-

jections consisted of intra-articular injections (Lilius 1990; Carette

1991; Marks 1992; Revel 1999; Mayer 2004; Fuchs 2005), peri-ar-

ticular injections (Lilius 1990; Revel 1999) or nerve blocks (Marks

1992; Manchikanti 2001). Local injections sites varied from ten-

der- and trigger points (Garvey 1989; Collee 1991) to mus-

cles (Mauro 2000) and ligaments (Sonne 1985). The drugs that

were studied were mostly corticosteroids (i.e. methylprednisolone,

triamcinolone and prednisolone) (Beliveau 1971; Breivik 1976;

Sonne 1985; Garvey 1989; Lilius 1990; Rocco 1989; Carette

1991; Marks 1992; Aldrete 2003; Mayer 2004; Fuchs 2005) or



local anesthetics (i.e. procaine, lidocaine, bupivacaine, lignocaine

and ropivacaine) (Collee 1991;Revel 1999; Lierz 2004; Takada

2005). Other drugs that were studied were non-steroidal anti-

inflammatories (NSAIDs) (Aldrete 2003), sodium hyaluronate

(Fuchs 2005), Sarapin (i.e. a suspension of powdered pitcher plant

in alkaline solution) (Manchikanti 2001), Vitamin B12 (Mauro

2000), morphine (Rocco 1989) and Midazolam (Serrao 1992).

Eight studies appeared to be placebo-controlled (Beliveau 1971;

Breivik 1976; Sonne 1985; Garvey 1989; Lilius 1990; Carette

1991; Collee 1991; Mauro 2000) and 10 to be studies that

compared injections with other treatments (Rocco 1989; Marks

1992; Serrao 1992; Revel 1999; Manchikanti 2001; Aldrete 2003;

Lierz 2004; Mayer 2004; Fuchs 2005; Takada 2005). Among the

placebo-controlled studies, three used an anesthetic (i.e. procaine,

bupivacaine and lidocaine) as part of their reference injections

(Beliveau 1971; Breivik 1976; Garvey 1989). Nevertheless, we still

considered these studies placebo-controlled since the experimental

treatments in these studies consisted of corticosteroids with a sim-

ilar amount of anesthetic added to the solution as in the reference

treatment. Anesthetics in general have a relatively short duration

of action and from a pharmacological standpoint it seems unlikely

that they will result in lasting pain relief (Nelemans 2000).

In two studies the authors declared they had received their drugs

from commercial companies (Breivik 1976; Carette 1991). The

authors of three other studies explicitly reported that they had

no financial conflict of interest (Fuchs 2005; Lilius 1990; Aldrete

2003). The authors of the other studies provided no explicit in-

formation in their publication about funding or eventual conflicts

of interest.

Risk of bias in included studies

For the assessment of the methodological quality of the trials, we

combined the information from all papers reporting on the same

trial. The two reviewers disagreed on 72 of 198 items (36%) scored.

After discussing the results, they reached consensus on the scoring

of all items. Therefore, the assistance of a third reviewer was not

needed. Nine of the 18 studies included met six or more internal

validity criteria and were therefore considered to be at an acceptable

level of methodological quality (Breivik 1976; Garvey 1989; Rocco

1989; Carette 1991; Collee 1991; Marks 1992; Revel 1999; Lierz

2004; Takada 2005). The most prevalent shortcomings were: a

lack of clarity regarding the concealment of random treatment

allocation (N = 17), no reporting of co-interventions (N = 14)

and no reporting of an intention-to-treat analysis (N = 13). The

internal validity criteria that were most frequently met were: the

acceptability of the level of compliance of patients to the treatment

protocol (N = 18), the description and acceptability of the drop-

out rate (N = 14) and the similarity of the timing of the outcome

assessments (N = 13). See details in Figure 1.



Figure 1. Summary of risks of bias



Effects of interventions

Feasibility of statistical pooling

As stated in the method section, statistical pooling was only con-

sidered if subgroups of studies were clinically homogeneous and

the authors provided sufficient information on study character-

istics, outcome measures and study results. After reviewing the

study characteristics of the studies included, only two subgroups

of two studies seemed to be sufficiently clinically homogeneous to

perform statistical pooling. Beliveau 1971 et al and Breivik 1976

et al compared the effect of epidural corticosteroid injections to

placebo injections and looked at short-term results of pain re-

lief, measured on a subjective dichotomous scale. However, in the

study by Breivik 1976 et al, the patients who were allocated to a

particular treatment and who did not improve were also treated

with injections of the alternative group. The timing of the out-

come measurements in this study was not clear either. Therefore,

we thought these two studies were too heterogeneous to pool their

results. Carette 1991 et al and Lilius 1990 et al compared the ef-

fects of facet joint injections with corticosteroids to placebo injec-

tions (Lilius 1990; Carette 1991). However, the study by Carette

1991 et al used a dichotomous outcome for pain improvement,

whereas Lilius 1990 et al reported mean pain scores and no pro-

portions of patients with pain relief. Therefore, it was not possible

to pool the results of these two studies. Consequently, instead of

statistical pooling, we had to perform a best-evidence synthesis for

both subgroups of studies.

Effectiveness of injection therapy

1. Epidural injections

Epidural corticosteroids versus placebo injections

Two studies compared the short term effects of epidural corti-

costeroid injections to placebo injections (Beliveau 1971; Breivik

1976). One of them was rated as a high quality study (Breivik

1976) and the other one was rated as a low quality study (Beliveau

1971). These two studies did not show a significant result for pain

relief or other outcomes in favour of the corticosteroids group.

There is limited evidence that epidural corticosteroid injections

are not significantly different from placebo injections for general

improvement in the short term (1 trial; 48 patients). There is

moderate for pain relief and limited evidence for work disability

that epidural corticosteroid injections are not significantly differ-

ent from placebo injections in the short term (1 trial; 35 patients).

Back-specific disability, generic health status and patient satisfac-

tion were not measured.

Epidural corticosteroid injections versus other treatments

Three studies compared the effects of epidural corticosteroid injec-

tions to other treatments. The low quality study by Aldrete 2003

et al compared corticosteroids to NSAIDs (i.e. indomethacin) and

showed no significant differences in short-term pain progress and

physical activity in post-laminectomy patients. In the low quality

study by Serrao 1992 et al, corticosteroids were combined with

dextrose solution and compared to an intrathecal benzodiazepine

(i.e. Midazolam) combined with a dextrose solution. No signifi-

cant differences between the groups were reported for pain relief

at two weeks and two months, or general improvement at two

months. In a high quality study, Rocco 1989 et al compared cor-

ticosteroids to morphine and to a combination of corticosteroids

and morphine in post-laminectomy patients but found no signif-

icant differences in pain relief at one or six months.

There is limited evidence that the effect of epidural corticosteroid

injections are not significantly different from NSAIDs for pain

relief in the short term in post-laminectomy patients (1 trial; 206

patients), benzodiazepine for pain relief and general improvement

both in the short and intermediate term (1 trial; 28 patients), and

from morphine eventually combined with corticosteroids for pain

relief in the short and intermediate term in post-laminectomy pa-

tients (1 trial; 22 patients). Back-specific disability, generic health

status, disability for work and patient satisfaction were not mea-

sured.

Epidural injections with local anaesthetics versus other

treatments

In a high quality study, Lierz 2004 et al compared the effects of

epidural blocks with ropivacaine to epidural blocks with bupi-

vacaine. The purpose of these blocks with local anaesthesia was

to provide good analgesia to allow active physiotherapy. There

were no significant differences found between the groups in post-

treatment analgesia. In a low quality randomized cross-over study,

Takada 2005 et al also investigated the effects of epidural blocks

with ropivacaine of two different dosages and epidural blocks of

bupivacaine. No significant differences in pain scores were found

after the different epidural blockades.

There is moderate evidence (2 trials; 56 patients) that there is no

significant difference in the amount of analgesia provided between

epidural blocks with ropivacaine and epidural blocks with bupi-

vacaine. General improvement, back-specific disability, generic

health status, disability for work and patient satisfaction were not

measured.

2. Facet joint injections



Facet joint injections with corticosteroids versus placebo

injections

One high quality study and one low quality study compared the

effects of facet joint injections with corticosteroids to placebo in-

jections. In their high quality study, Carette 1991 et al pre-se-

lected and only included patients who responded positively to a

facet joint injection with lidocaine (more than 50% reduction in

pain score). These patients were randomly allocated to either cor-

ticosteroids or placebo injections. No significant differences for

self-rated improvement, pain or functional status were found be-

tween the groups at one and three months. At six months, sig-

nificant differences were found with regard to self-rated improve-

ment, pain and functional status in favour of the corticosteroids

group (Carette 1991). In a low quality study, Lilius 1990 et al com-

pared corticosteroids injected intra-articularly to corticosteroids

injected peri-capsularly and to placebo injections. No significant

differences between the groups were reported for pain, disability

and work attendance at one hour, two weeks, six weeks and three

months (Lilius 1990).

There is moderate evidence (2 trials; 210 patients) that facet joint

injections with corticosteroids are not significantly different from

placebo injections for short term pain relief and improvement

of disability. There is conflicting evidence (2 trials; 210 patients)

whether facet joint injections with corticosteroids are more effec-

tive for intermediate term pain reduction and improvement of dis-

ability than placebo injections. There is limited evidence (1 trial;

109 patients) that there is no significant difference between the

effects of facet joint injections with corticosteroids and placebo

injection on work attendance. Generic health status and patient

satisfaction were not measured.

Facet joint injections with corticosteroids versus other

treatments

In four studies, the effects of corticosteroids injections into the

facet joints were compared with other treatments. In a low quality

study, Manchikanti 2001 et al compared the effects of multiple

medial branch blocks, consisting of corticosteroids combined with

local anaesthetics and Sarapin, to multiple medial branch blocks

consisting of only local anaesthetics and Sarapin. No significant

differences between the groups were found in pain relief, overall

health, physical, functional, and psychological status and return-

to-work at different follow-up moments throughout a 2.5-year

follow-up period. In a low quality study, Mayer 2004 et al made

a comparison between facet joint injections on one to three levels

bilaterally, with mixtures of local anaesthetics and corticosteroids

combined with a home stretching exercise program, and the home

stretching exercise program only. No significant post-treatment

differences between the groups were found for pain and disabil-

ity. In the high quality study by Marks 1992 et al, facet joint in-

jections with corticosteroids and lignocaine were compared with

facet nerve blocks using similar medication. The facet joint injec-

tions provided slightly better pain relief than facet nerve blocks,

although statistical significance was only reached at one month,

not immediately post-treatment, at two weeks or three months

(Marks 1992). In a low quality study, Fuchs 2005 et al compared

the effects of facet joint injections with sodium hyaluronate to

similar injections with corticosteroids. No significant differences

in pain relief, disability and quality of life between the groups were

found at different follow-up points over a 180-day period.

There is limited evidence (1 trial; 84 patients) that facet joint injec-

tions consisting of corticosteroids, local anaesthetics and Sarapin

are not more effective than similar injections, consisting of local

anaesthetics and Sarapin, in influencing pain relief, overall health,

physical, functional, psychological status and return-to-work at

short- and long- term follow-up. There is limited evidence (1 trial;

70 patients) that facet joint injections with mixtures of corticos-

teroids and local anaesthetics combined with a home stretching

exercise program are not more effective than a home stretching

exercise program alone in providing long term effects on pain and

disability. There is moderate evidence (1 trial; 86 patients) that

facet joint injections with corticosteroids and local anaesthetics are

not more effective in improving short- and long-term pain scores,

disability scores and work attendance than facet nerve blocks using

similar medication. There is limited evidence (1 trial; 60 patients)

that facet joint injections with sodium hyalorunate are not more

effective than similar injections with corticosteroids in providing

short- and long- term pain relief, better function and improved

quality of life. Patient satisfaction was not measured.

Facet joint injections with local anaesthetics versus other

treatments.

One high quality study by Revel 1999 et al, which was designed

from a diagnostic perspective, compared facet joint injections with

lidocaine to facet joint injections with saline. In both groups these

injections were followed by an injection with corticosteroids (i.e.

cortivazol) near the joints. The lidocaine group had significantly

higher pain relief post-treatment than the saline group (Revel

1999).

There is moderate evidence (1 trial; 80 patients) that facet joint in-

jections with lidocaine combined with peri-articular corticosteroid

injections are more effective for short-term pain relief than facet

joint injections with saline combined with peri-articular corticos-

teroid injections. General improvement, back-specific disability,

generic health status, disability for work and patient satisfaction

were not measured.

3. Local injections

Local injections with corticosteroids versus placebo

injections



In a high quality study, Garvey 1989 et al compared trigger point

injections with corticosteroids (i.e. Aristopan) to placebo injec-

tions, a dry needle stick (acupuncture) and a spray of ethylchlo-

ride and acupressure in patients with persistent non-radiating low-

back pain, who were able to localize a point of maximal tender-

ness. No significant differences between the groups in self-reported

improvements were found at two weeks. In a low quality study,

Sonne 1985 et al studied the effects of local iliolumbar ligament

injections with corticosteroids versus placebo and found no sig-

nificant differences in pain relief at two weeks. However, self-re-

ported improvement at two weeks was significantly higher in the

corticosteroid group than in the placebo group (Sonne 1985).

There is moderate evidence (1 trial; 63 patients) that trigger point

injections with corticosteroids are not significantly different from

placebo injections for self-reported improvements at short-term

follow-up. There is limited evidence (1 trial; 30 patients) that local

injections into the iliolumbar ligament are more effective than

placebo for self-reported improvement in the short term but not

for pain relief in the short term. Back-specific disability, generic

health status, disability for work and patient satisfaction were not

measured.

Local injections with anaesthetics versus placebo injections

The high quality study by Collee 1991 et al investigated the effects

of a single local injection of lignocaine into the point of maximal

tenderness over the medial part of the iliac crest versus a placebo

injection. At two weeks, the mean pain score was significantly

lower in the lignocaine groups compared to the placebo group. A

non-significant difference in favour of the lignocaine group was

also found for self-reported improvement (Collee 1991).

There is moderate evidence (1 trial; 41 patients) that an injection

with a local anaesthetic at the point of maximal tenderness over

the medial part of the iliac crest, in patients with iliac crest pain

syndrome is more effective for short-term pain relief than a placebo

injection. Back-specific disability, generic health status, disability

for work and patient satisfaction were not measured.

Intramuscular injections with Vitamin B12 versus placebo

injections

In a low quality study, Mauro 2000 et al compared the effects of

intramuscular Vitamin B12 injections to intramuscular placebo

injections and found significant effects for post-treatment pain

and disability in favour of the Vitamin B12 group.

There is limited evidence (1 trial; 60 patients) that intramuscu-

lar Vitamin B12 injections are more effective than intramuscu-

lar placebo injections for short-term pain relief and disability im-

provement. Generic health status, disability for work and patient

satisfaction were not measured.

Clinical relevance

There was disagreement between the two review authors with re-

gard to the scoring of 27 of 90 (30%) clinical relevance items

(Table 3). Consensus was reached on all scorings after discussion.

In only two studies, the review authors considered the likely treat-

ment benefits to be worth the potential harms (Revel 1999; Mauro

2000) and in only four studies, the size of the effect was considered

to be clinically important (Breivik 1976; Sonne 1985; Revel 1999;

Mauro 2000). According to the review authors, most of the studies

described the interventions and treatment settings well enough to

enable clinicians to replicate the treatment in clinical practice.

Side effects

In nine of the 18 studies, side effects such as headache, dizziness,

transient local pain, paresthesia and nausea were reported in small

numbers of patients (Table 2). The use of morphine was more

frequently associated with pruritis, nausea and vomiting (Rocco

1989).

D I S C U S S I O N

The overall methodological quality of the studies included in this

review was limited and only six of the 18 trials (Sonne 1985;

Collee 1991; Carette 1991; Marks 1992; Revel 1999; Mauro

2000) showed significant results for at least one outcome at a fol-

low-up time point in favour of one of the treatment arms. Four

of these six studies reported effects that could be considered to

be clinically important (Breivik 1976; Mauro 2000; Revel 1999;

Sonne 1985). We conclude there is no strong evidence to support

the use of any type of injection therapy (epidural, facet joint or

local sites) for subacute or chronic-low-back pain in patients with-

out radicular pain. In the earlier Cochrane review on this topic,

Nelemans 2000 et al also concluded that convincing evidence was

lacking on the effects of injection therapy for low-back pain, which

means that the general picture on the effectiveness of injection

therapy has not changed since then. The scientific basis for these

injections for low-back pain has not improved.

Nelemans 2000 et al proposed several recommendations for fu-

ture research. These recommendations involved the priority for

placebo-controlled trials instead of trials that compared injections

to other treatments, the need for methodologically sound RCTs,

and more of a focus on long-term effects of the treatment in-

stead of only short-term effects (Nelemans 2000). Among the 18

studies included in this review, seven new studies were covered

in the present update (Mauro 2000; Manchikanti 2001; Aldrete

2003; Lierz 2004; Fuchs 2005; Takada 2005 ). Of these seven new

studies, only Mauro 2000 et al compared intramuscular Vitamin

B12 with placebo injections, which resulted in a total of seven



placebo-controlled versus 12 studies that compared injections to

other treatments or to each other.

According to the methodological quality assessment, the new stud-

ies in this update had no higher methodological quality than the

studies of the earlier review. On the contrary, the mean number

of positive items was even lower (4.1 versus 6.3 positive scores;

Table 2; Table 3) in this group of studies compared to the studies

included in the earlier review. The most prevalent shortcomings,

which were a lack of clarity regarding the concealment of ran-

dom treatment allocation, no reporting of co-interventions and

no reporting of an intention-to-treat analysis, could easily have

been avoided and nowadays, researchers should be aware that

these are generally accepted principles of methodological qual-

ity for studying the effectiveness of treatments. Only four out of

the 18 studies included had outcome assessments performed at

six months post-randomization and beyond (Rocco 1989; Carette

1991; Manchikanti 2001; Fuchs 2005). The outcome assessments

of the other studies were either performed post-treatment or at

another short-term time interval. Of course, from a pharmaco-

logical standpoint, the agent under study may act upon the tar-

get tissue rather quickly, for example, by reducing inflammation.

However, it is advantageous that the favourable effects on pain

and disability will also stand at the longer term. Since the course

of sub-acute and chronic low-back pain can be described as con-

sisting of spontaneous remissions and exacerbations (Croft 1998)

short-term effects of injections do not necessarily reflect a success-

ful treatment result in clinical practice. Outcome measures which

were used in the studies included visual analogues scales for pain

relief and questions regarding self-perceived improvement or other

outcomes. Only six studies used well-known and validated ques-

tionnaires for measuring disability (Rocco 1989; Carette 1991;

Serrao 1992; Mauro 2000 ; Mayer 2004; Fuchs 2005).

For the purpose of this review, we subdivided the studies accord-

ing to injection sites (i.e. epidural, facet joint and local sites),

to pharmaceutical agents (i.e. corticosteroids, anaesthetics and

other agents) and according to the comparison that was made (i.e.

placebo-controlled versus comparison of two or more treatments).

By following this approach, our aim was to come up with groups

that were clinically comparable without ending up with groups

consisting of only one study. Despite the fact that this approach

seemed logical, there were still differences among the studies that

ended up in a group with regard to inclusion criteria, target tis-

sue (e.g. intra-articular facet joint injections, peri-capsular facet

joint injections and medial branch blocks), injection dosage, co-

interventions, reference treatments and outcome measures. This

should be kept in mind when reading the evidence statements in

the results section of this paper. Furthermore, it should be empha-

sized that we only separated trials on the basis of whether the com-

parator was a placebo injection or other treatment. Other aspects

of the studies, such as meticulous patient selection by diagnostic

injections or experience and skills of the treatment providers were

not assessed.

One of the main problems when studying the effects of injec-

tion therapy in low-back pain is the lack of diagnostic criteria for

determining the injection site. According to our view, it is ex-

tremely difficult to accurately diagnose and determine the local-

isation of tissues that cause the pain and other symptoms. Some

researchers have tackled this problem, for example, by only includ-

ing patients for facet joint injections who responded positively to

facet blocks with anaesthetics (Carette 1991; Manchikanti 2001)

or patients with radiologically confirmed facet joint osteoarthritis

(Fuchs 2005). From these three studies, only the study by Carette

1991 et al had positive results. They showed significant effects for

pain and the physical dimension of the Sickness Impact Profile

in favour of a methylprednisolone group compared to a placebo

group, even after six-month follow-up (Carette 1991).

The rationale behind the application of a particular pharmaceu-

tical agent among the included studies was variable. In 13 stud-

ies, the effects of corticosteroids were investigated. This may be a

reasonable choice since this agent aims to reduce inflammation.

In four studies, the main pharmaceutical agent under study was

anaesthetics (Collee 1991; Revel 1999; Lierz 2004; Takada 2005).

The reason for choosing an injection with anaesthetics is not al-

ways immediately clear. Due to the relatively short duration of

action of these pharmaceutical agents, they do not seem to be the

first choice for pain relief in sub-acute and chronic patients. Lierz

2004 et al and Takada 2005 et al compared the short- term anal-

gesic effects of epidural blocks with ropivacaine and bupivacaine

and found no significant differences between the groups. The au-

thors of both studies explained that epidural blocks may provide

analgesia to allow for exercise and active physiotherapy, thus facil-

itating more active therapies. Collee 1991 et al compared a local

injection of lignocaine versus saline into a tender point over the

medial part of the iliac crest. The study authors state that the in-

jection with lignocaine may somehow affect the ascending or sen-

sory input and its varying modulating systems. However, no sig-

nificant differences in improvement rates were found. The study

by Revel 1999 et al was carried out from a diagnostic perspective.

They compared facet joint injections with lidocaine to placebo

injections in order to determine several clinical criteria which were

predictive of significant relief of back pain after facet joint anaes-

thesia (Revel 1999). Other applied pharmaceutical agents were:

indomethacin (Aldrete 2003), sodium hyaluronate (Fuchs 2005),

Sarapin (Manchikanti 2001), morphine (Rocco 1989) and Vita-

min B12 (Mauro 2000). In the study by Mauro 2000 et al, daily

intramuscular injections for a two-week period with Vitamin B12

appeared to be effective for short-term pain and disability com-

pared to placebo injections.

Half of the included studies reported side effects in small numbers

of patients (see Characteristics of included studies table). These side



effects ranged from headache, dizziness and transient local pain

to nausea and vomiting. Although these are not life threatening

complications and have only been reported in a limited number

of patients, this does not mean that the application of injection

therapy in low-back pain is always without risk. Rare but more

serious complications of injection therapy have been mentioned in

the literature, such as, cauda equina syndrome (Bilir 2006), septic

facet joint arthritis (Weingarten 2006), discitis (Hooten 2006),

paraplegia (Houten 2002) and paraspinal abscesses (Cook 1999).

In another study, it was found that eight out of 128 consecutive

patients referred to a hospital with meningitis had a history of sin-

gle or repeated injections for low-back pain one to three weeks be-

fore their hospital admission (Gaul 2005). Although the absolute

frequency of these complications may be rare, these risks should be

taken into consideration, especially given the fact that convincing

evidence on the effects of injection therapy for low-back pain is

still lacking.

Seven out of the 18 trials included in this review reported signifi-

cant but short-lasting effects in favour of the intervention group,

with interventions varying from facet joint injections with cor-

ticosteroids (Carette 1991; Mayer 2004) and anaesthetics (Revel

1999), epidural injections with corticosteroids (Breivik 1976), lo-

cal injections with anaesthetics (Sonne 1985; Collee 1991) to

intramuscular injections with Vitamin B12 (Mauro 2000). The

overall picture of the results of this review reveals that there is

currently insufficient scientific evidence on the effects of injec-

tion therapy, regardless of type and dosage, for patients with sub-

acute and chronic low-back pain. It is discouraging that the aver-

age methodological quality of the trials published since the earlier

review has not improved while the validity criteria for effective-

ness research have become more familiar to back pain researchers.

Most studies dealt with heterogeneous groups of patients, which

on average, may mask potential treatment effects. Therefore, we

can not rule out that some type of injection therapy might be

effective for a particular subgroup of patients. Therefore, accu-

rate diagnostic criteria are needed. However, this remains merely a

theoretical consideration, which is not based on the results of the

present review.

A U T H O R S ’ C O N C L U S I O N S

Implications for practice

Based on the current state of the literature there is insufficient

evidence to support or refute the use of injection therapy, regardless

of type and dosage, for patients with subacute and chronic low-

back pain without radicular pain.

Implications for research

We can not rule out that some type of injection therapy is effective

for a particular subgroup of patients. More research is needed to

study the accuracy of diagnostic criteria to identify which, if any,

subgroups of patients are likely to respond to injection therapy

and if established, the effectiveness of injection therapy for these

subgroups. Corticosteroids seem to be the most logical therapeutic

agent, while anaesthetics seem only useful for diagnostic purposes.

If injection therapy turns out to be an effective treatment strategy

for a subgroup of low-back pain patients, it has to be embedded

in the current, widely supported active approach directed at reas-

surance and self management.

A C K N O W L E D G E M E N T S

The review team wishes to thank Professor Ferd Sturmans, The

Netherlands, for his contribution to the original review.

R E F E R E N C E S

References to studies included in this review

Aldrete 2003 {published data only}∗ Aldrete JA. Epidural injections of indomethacin for

postlaminectomy syndrome: a preliminary report. Anesth

Analg 2003;96(2):463–8.

Beliveau 1971 {published data only}

Beliveau P. A comparison between epidural anaesthesia with

and without corticosteroid in the treatment of sciatica.

Rheumatol Phys Med 1971;11(1):40–3.

Breivik 1976 {published data only}

Breivik HH, Hesla PE, Molnar I, Lind B. Treatment of

chronic low back pain and sciatica: comparison of caudal

epidural injections of bupivacaine and methylprednisolone

with bupivacaine followed by saline. Adv Pain Res Ther

1976;1:927–32.

Carette 1991 {published data only}∗ Carette S, Marcoux S, Truchon R, Grondin C, Gagnon J,

Allard Y, et al.A controlled trial of corticosteroid injections

into facet joints for chronic low back pain. N Eng J Med

1991;325(14):1002–7.

Collee 1991 {published data only}

Collee G, Dijkmans BA, Vandenbroucke JP, Cats A. Iliac

crest pain syndrome in low back pain. A double blind,

randomized study of local injection therapy. J Rheumatol

1991;18(7):1060–3.

Fuchs 2005 {published data only}

Fuchs S, Erbe T, Fischer HL, Tibesku CO. Intraarticular



hyaluronatica acid versus glucocorticoid injections for

nonradicular pain in the lumbar spine. J Vasc Interv Radiol

2005;16(11):1493–8.

Garvey 1989 {published data only}

Garvey TA, Marks MR, Wiesel SW. A prospective,

randomized, double-blind evaluation of trigger point

injection therapy for low back pain. Spine 1989;14(9):

962–4.

Lierz 2004 {published data only}

Lierz P, Gustorff B, Markow G, Felleiter P. Comparison

between bupivacaine 0.125% and ropivacaine 0.2% for

epidural administration to outpatients with chronic low

back pain. Eur J Anaesthesiol 2004;21(1):32–7.

Lilius 1990 {published data only}

Lilius G, Harilainen A, Laasonen EM, Myllynen P. Chronic

unilateral low-back pain. Predictors of outcome of facet

joint pain. Spine 1990;15(8):780–2.

Lillius G, Laasonen EM, Myllynen P, Harilainen A,

Gronlund G. Lumbar facet joint syndrome. A randomised

clinical trial. J Bone Joint Surg 1989;71:681–4.

Lillius G, Lassonen AM, Myllynen P, Harilainen A, Salo

L. The lumbar facet joint syndrome: significance of

inappropriate signs: a randomized, placebo-controlled trial.

French Journal of Orthopaedic Surgery 1989;3(4):479–86.

Manchikanti 2001 {published data only}

Manchikanti L, Pampati V, Bakhit C, Rivera JJ, Beyer CD,

Damron KS, et al.Effectiveness of lumbar facet joint nerve

blocks in chronic low back pain: a randomized clinical trial.

Pain Physician 2001;4(1):101–7.

Marks 1992 {published data only}

Marks RC, Houston T, Thulbourne T. Facet joint injection

and facet nerve block: a randomised comparison in 86

patients with chronic low back pain. Pain 1992;49(3):

325–8.

Mauro 2000 {published data only}

Mauro GL, Martorana U, Cataldo P, Brancato G, Letizia G.

Vitamin B12 in low back pain: a randomised, double-blind

placebo-controlled study. Eur Rev Med Pharmacol Sci 2000;

4(3):53–8.

Mayer 2004 {published data only}

Mayer TG, Gatchel RJ, Keeley J, McGeary D, Dersh J,

Anagnostis C. A randomized clinical trial of treatment for

lumbar segmental rigidity. Spine 2004;29(20):2199–2205.

Revel 1999 {published data only}

Revel M, Poiraudeau S, Auleley GR, Payan C, Nguyen

M, Chevrot A, et al.Capacity of the clinical picture to

characterize low back pain relieved by facet joint anesthesia.

Proposed criteria to identify patients with painful facet

joints. Spine 1998;23(18):1972–6.

Rocco 1989 {published data only}

Rocco AG, Frank E, Kaul AF, Lipson SJ, Gallo JP. Epidural

steroids, epidural morphine and epidural steroids combined

with morphine in the treatment of post-laminectomy

syndrome. Pain 1989;36(3):297–303.

Serrao 1992 {published data only}

Serrao JM, Marks RL, Morley SJ, Goodchild CS. Intrathecal

midazolam for the treatment of chronic mechanical low

back pain: a controlled comparison with epidural steroid in

a pilot study. Pain 1992;48(1):5–12.

Sonne 1985 {published data only}

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of steroids and local anaesthetics as therapy for low back

pain. Scand J Rheumatol 1985;14(4):343–5.

Takada 2005 {published data only}

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C, Sumikawa K. Comparative efficacy of ropivaciane

and bupivacaine for epidural block in outpatients with

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Bonetti M, Fontana M, Cotticelli B, Volta GD, Guidani M,

Leonardi M. Intraforaminal O2-O3 versus periradicular

steroidal infiltrations in lower back pain: Randomized

controlled study. AJNR Am J Neuroradiol 2005;26(5):

996–1000.

Bush 1991 {published data only}

Bush K, Hillier S. A controlled study of caudal epidural

injections of triamcinolone plus procaine for the

management of intractable sciatica. Spine 1991;16(5):

572–5.

Cuckler 1985 {published data only}

Cuckler JM, Bernini PA, Wiesel SW, Booth RE, Rothman

RH, Pickens GT. The use of epidural steroids in the

treatment of lumbar radicular pain. A prospective

randomized, double-blind study. J Bone Joint Surg Am

1985;67(1):63–6.

Dallas 1987 {published data only}

Dallas TL, Lin RL, Wu WH, Wolskee P. Epidural morphine

and methylprednisolone for low back pain. Anesthesiology

1987;67(3):408–11.

Fredman 1999 {published data only}

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Gepstein R. The effect of repeated epidural sympathetic

nerve block on “failed back surgery syndrome” associated

chronic low back pain. J Clin Anesth 1999;11(1):46–51.

Glynn 1988 {published data only}∗ Glynn C, Dawson D, Sanders R. A double-blind

comparison between epidural morphine and epidural

clonidine in patients with chronic non-cancer pain. Pain

1988;34(2):123–8.

Hameroff 1981 {published data only}

Hameroff SR, Crago BR, Womble J, Kanel J. Comparison

of bupivacaine, etidocaine, and saline for trigger point

therapy. Anesth Analg 1981;60(10):752–5.

Mathews 1987 {published data only}

Mathews JA, Mills SB, Jenkins VM, Grimes SM, Morkel

MJ, Mathews W, et al.Back pain and sciatica: controlled



trials of manipulation, traction, sclerosant and epidural

injections. Br J Rheumatol 1987 26;6:416–23.

Ney 2006 {published data only}

Ney JP, Difazio M, Sichani A, Monacci W, Foster L,

Jabbari B. Treatment of chronic low back pain with

succesive injections of Botulinum Toxin A over 6 months:

a prospective trial of 60 patients. Clin J Pain 2006;22(4):

363–9.

Ofluoglu 2007 {published data only}

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calcitonin on beta-emdorphin levels in postmenopausla

osteoporotic patients with back pain. Clin Rheumatol 2007;

26(1):44–9.

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Oh WS, Shim JC. A randomized controlled trial of

radiofrequency denervation of the ramus communicans

nerve for chronic discogenic low back pain. Clin J Pain

2004;20(1):55–60.

Ongley 1987 {published data only}

Ongley MJ, Klein RG, Dorman TA, Eek BC, Hubert LJ. A

new approach to the treatment of chronic low back pain.

Lancet 1987;2(8551):143–6.

Pneumaticos 2006 {published data only}

Pneumaticos SG, Chatziioannou SN, Hipp JA, Moore WH,

Esses SI. Low back pain: prediction of short-term outcome

of facet joint injection with bone scintigraphy. Radiology

2006;238(2):693–8.

Rogers 1992 {published data only}

Rogers P, Nash T, Schiller D, Norman J. Epidural steroids

for sciatica. Pain Clin 1992;5(2):67–72.

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low back pain. Joint Bone Spine 2003;70(5):356–61.

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References to other published versions of this review

Nelemans 2000

Nelemans PJ, de Bie RA, de Vet HCW, Sturmans F.

Injection therapy for subacute and chronic low back pain.

Cochrane Database of Systematic Reviews 2000, Issue 2.

[DOI: 10.1002/14651858]∗ Indicates the major publication for the study



C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of included studies [ordered by study ID]

Aldrete 2003

Methods RCT; Randomization procedure not described.

Participants Pain care center, Florida, USA.

206 patients with recurrent LBP and radiculopathy after laminectomy, at least 6 months

post operation, lower back and extremity pain > 7 points on VAS scale (0 to 10). The

duration of pain was not specified. Exclusion criteria: pseudomeningocele, arachnoiditis

and/or recurrent pain from free disk fragments as confirmed by MRI study

Interventions (1) 2 epidural injections of indomethacin 1 mg.

(2) 2 epidural injections of indomethacin 2 mg.

(3) 2 epidural injections of methylprednisolone 80 mg.

In every case, the interval between the injections was 2 weeks and medication was diluted

in 3 ml of 0.5% bupivacaine

Outcomes Timing of outcomes: before and 2 weeks after randomization.

No significant differences were reported between the groups in pain progress and physical

activity at 2 weeks

Notes Side-effects: no instances of apparent dural puncture or high sensory or motor block

were noted, nor were other effects typical of NSAIDs therapy such as rash, epigastric

discomfort, or bruising

Risk of bias

Bias Authors’ judgement Support for judgement

Adequate sequence generation? Unclear risk Randomization procedure not described

Allocation concealment? Unclear risk B - Unclear

Blinding?

All outcomes - patients?

Unclear risk unclear from text

Blinding?

All outcomes - care providers?

High risk no

Blinding?

All outcomes - outcome assessors


Incomplete outcome data addressed?

All outcomes - drop-outs?

High risk



Aldrete 2003 (Continued)


All outcomes - ITT analysis

High risk

Similarity of baseline characteristics? Unclear risk unclear from data given

Co-interventions avoided or similar? Unclear risk unclear from text

Compliance acceptable? Low risk

Timing outcome assessments similar? Low risk

Beliveau 1971

Methods RCT; Patients were allocated alternately to treatment groups

Participants Department of Rheumatology and Physical medicine, UK.

48 patients with unilateral sciatica, thought to be caused by an intervertebral disc lesion,

with or without neurological signs, before or after other conservative treatments had

been tried. The duration of pain was not specified

Interventions (1) Epidural injection of 42 ml of procaine 0.5% in normal saline.

(2) Epidural injection of 40 ml of procaine 0.5% in normal saline to which 2 ml of

methylprednisolone 80 mg had been added.

In both groups injections were repeated in patients who had an improvement after the

first injection

Outcomes Timing of outcomes: before and 1 week after randomization.

(1) 16 of 24 patients improved at 1 week after the injection; (2) 18 of 24 patients

improved at 1 week after the injection; no other outcomes reported

Notes Side effects: Mild headache and dizziness occurred in about ten cases; the symptoms

were transient lasting up to 30 minutes after the injection. In two cases the theca was

penetrated by the needle during the injection and the procedure was stopped

Risk of bias


Adequate sequence generation? High risk Patients were allocated alternately to treat-

ment groups

Allocation concealment? High risk C - Inadequate

Blinding?


High risk



Beliveau 1971 (Continued)

Blinding?


High risk

Blinding?


High risk



Low risk



Low risk

Similarity of baseline characteristics? High risk

Co-interventions avoided or similar? High risk



Breivik 1976

Methods RCT; Patients were allocated according to a list of random numbers

Participants Departments of Anesthesiology and Neurology, Akershus Central Hospital and outpa-

tient clinic, Norway

35 patients with incapacitating chronic low-back pain and sciatica unresponsive to con-

servative treatment for several months to several years. Diagnoses based on radiculogra-

phy: arachnoiditis (N=8), prolapsed disc (N=8), no abnormality (N=11), inconclusive

findings (N=5)

Interventions (1) Caudal epidural injection of 20 ml bupivacaine 0.25% with 80 mg depo-methyl-

prednisolone.

(2) Caudal epidural injection of 20 ml bupivacaine 0.25% followed by 100 ml saline.

Frequency: up to three injections at weekly intervals eventually followed by up three

injections of the alternative group

Outcomes Timing of outcomes: 2 to 5 weeks after randomization

Reported outcomes were pain relief, objective improvements (i.e. neural symptoms) and

work status.

Pain relief was obtained in 63% of the patients in the intervention group and 68% of

the patients in the reference group which was no statistically significant difference

Notes If there was no improvement 3 weeks after the last injection, up to three injections of

the alternative type were given. Side effects: not mentioned

Risk of bias



Breivik 1976 (Continued)


Adequate sequence generation? Low risk Patients were allocated according to a list

of random numbers


Blinding?


Low risk

Blinding?


High risk

Blinding?


Low risk



Low risk



High risk

Similarity of baseline characteristics? Unclear risk data not provided

Co-interventions avoided or similar? Low risk


Timing outcome assessments similar? High risk

Carette 1991

Methods RCT; Randomization by random numbers generation, balancing after every 8 patients

Participants Centre Hospitalier de l’Université Laval, Quebec city, Canada.

101 patients with pain originating in the facet joints and who had a >50% reduction

(on a VAS score for pain) after injection with lidocaine were entered into the trial.

The mean duration of the current episode of pain was 18 (intervention group) and 24

months (control group). Exclusion criteria: back pain with a non mechanical origin,

previous injections in the facet joints or surgery, pregnancy, known allergy to anesthetic

or radiological contrast agents, presence of a blood coagulation disorder

Interventions (1) Facet joint injection of 20 mg (1 ml) of methylprednisolone acetate mixed with 1 ml

isotonic saline.

(2) Facet joint injection of 2 ml isotonic saline.



Carette 1991 (Continued)

Outcomes Timing of outcomes: before and 1, 3 and 6 months after randomization and treatment.

At one and three months there were no significant differences in pain, functional status

and back flexion between the groups. At one month 42% of the patients in the methyl-

prednisolone group and 33% of the patients in the placebo group reported marked or

very marked improvement. At 6 months 46% of the patients in the methylprednisolone

group and 15% of the patients in the placebo group reported a significant marked or very

marked improvement. Significant differences at 6 months in favor of the methylpred-

nisolone group were also found for pain (VAS-score) and the physical dimension of the

Sickness Impact Profile. The differences were reduced when concurrent interventions in

the methylprednisolone group were taken into account

Notes Side effects: No adverse effects were reported, other than transient local pain at the

injection site

Risk of bias


Adequate sequence generation? Low risk Randomization by random numbers gen-

eration, balancing after every 8 patients


Blinding?


Low risk

Blinding?


Low risk

Blinding?


Low risk



Low risk



High risk

Similarity of baseline characteristics? Low risk






Collee 1991

Methods RCT; Randomization procedure not described

Participants Department of Rheumatology, University Hospital Leiden, The Netherlands. Patients

recruited from a university based outpatient clinic (median duration of pain was 8 years)

and a large general practice in a rural area (median duration of pain was 18 days).

41 patients with iliac crest pain syndrome. Exclusion criteria were: diagnosis of sciatica,

ankylosing spondylitis, malignancy, infection, spondylolysthesis, severe degenerative disc

disease or fibromyalgia

Interventions Single local injection at the point of maximal tenderness over the medial part of the iliac

crest.

(1) Injection of 5 ml lignocaine 0.5%.

(2) Injection of 5 ml isotonic saline.

Outcomes Timing: at baseline and 10 minutes, 7 days, 14 days and 2 months after the injection.

At 14 days the mean pain score in the lignocaine group was significantly lower than in the

control group. In the lignocaine group 52% of patients improved at 14 days compared to

30% in the control group. This difference was not statistically significant. Among those

who improved with lignocaine, the beneficial effect continued for at least 2 months in

80% of the patients

Notes Side effects: 2 patients in the lignocaine group and 3 in the saline group complained of

a painful injection or increase of pain for some hours after the injection. Nausea some

hours after the injection occurred in 2 of the patients treated with lignocaine and in 1

patient treated with saline

Risk of bias




Blinding?


Low risk

Blinding?


Low risk

Blinding?


Low risk



Low risk



Low risk



Collee 1991 (Continued)





Fuchs 2005

Methods RCT; block randomization, blocks of 6 patients generated by computer

Participants Private orthopedic practice, Goesfeld, Germany

60 patients with chronic non-radicular low-back pain (> 3 months) and with radiologic

confirmation of facet joint osteoarthritis

Interventions Injections into the facet joints at three levels of the lumber spine presumably most affected

by degenerative changes. Injections under CT guidance at weekly intervals. Each patient

received 6 injections.

(1) Injection of 10 mg sodium hyaluronate in 1 ml buffer solution.

(2) Injection of 10 mg glucocorticoids (triamcolone acetonide) in 1 ml crystalline sus-

pension

Outcomes Timing of outcomes: before and 7, 14, 21, 28, 90 and 180 days after randomization.

Both groups improved and had pain relief, better function and improved quality of life.

No statistically significant differences between the groups in outcomes were reported

Notes No adverse effects were reported after administration of both therapies

Risk of bias


Adequate sequence generation? Low risk block randomization, blocks of 6 patients

generated by computer


Blinding?


High risk

Blinding?


High risk

Blinding?





Fuchs 2005 (Continued)



Low risk



High risk





Garvey 1989

Methods RCT; Allocation by computer-generated four-tier list.

Participants Department of Orthopedic Surgery, The George Washington University Medical Center,

Washington DC.

63 patients with persistent non-radiating low-back pain (> 4 weeks) who were able to

localize a point of maximal tenderness

Interventions Trigger-point injections:

(1) 1.5 ml lidocaine 1%.

(2) 0.75 ml lidocaine 1% and 0.75 ml Aristopan (20 mg/ml).

(3) Dry needle stick (acupuncture).

(4) 10 second spray of ethylchloride and 20 second acupressure

Outcomes Timing of outcomes: patients were followed at 2-week intervals.

Therapy without injected medication (63% improvement rate) was at least as effective as

therapy with drug injection (42% improvement rate). The differences in improvement

rates between the groups were not statistically significant

Notes Side effects: One patient who received lidocaine plus steroid complained about increased

pain as well as two patients who received a dry needle stick. Another patient in the dry

needle group had complaints of fever, chills and systemic upset on the night of therapy

Risk of bias


Adequate sequence generation? Low risk Allocation by computer-generated four-

tier list




Garvey 1989 (Continued)

Blinding?


Low risk

Blinding?


Low risk

Blinding?


Low risk



Low risk



Low risk




Timing outcome assessments similar? Unclear risk not clearly stated in text

Lierz 2004

Methods RCT; Randomization performed by computer, no further description of procedure

Participants Department of Anaesthesiology and Intensive Care, Hospital, Soest, Germany

40 patients with low-back pain for at least 6 months.

Interventions Eight single shot epidural blocks at an interval of 2 or 3 days. Active physiotherapy was

performed immediately after each session.

(1) 10 ml ropivacaine 0.2%.

(2) 10 ml bupivacaine 1.125%.

Outcomes Timing of outcomes: before and post-treatment.

Both groups showed no significant differences in analgesia post-treatment

Notes Side effects: no significant differences were reported in hemodynamic variables; there

were three cases of short episodes of headache, two in the ropivacaine group and one in

the bupivacaine group

Risk of bias




Lierz 2004 (Continued)

Adequate sequence generation? Low risk Randomization performed by computer,

no further description of procedure


Blinding?


Low risk

Blinding?


Low risk

Blinding?


Unclear risk not stated in text



Low risk



High risk





Lilius 1990


Participants Department of Physical Medicine and Rehabilitation, Helsinki University Central Hos-

pital.

109 patients with low-back pain for over three months localized to one side with tender-

ness and local muscle spasm over the facet joints. 27 of them had undergone previous

disc surgery

Interventions One facet joint injection:

(1) 6 ml (30 mg) bupivacaine hydrochloride mixed with 2 ml (80 mg) methylpred-

nisolone acetate was injected into each of the two facet joints.

(2) The same mixture was injected pericapsularly around the facet joints.

(3) 8 ml of physiological saline was injected into the two joints

Outcomes Timing of outcomes: before and one hour, 6 weeks and 3 months after the injection.

All groups improved in work attendance, pain and disability scores. No significant dif-

ferences between the groups were found at one hour, 2 weeks, 6 weeks and 3 months



Lilius 1990 (Continued)

Notes Side effects: 7 of the 109 patients reported side effects. The nature of the side effects was

not reported

Risk of bias




Blinding?


High risk

Blinding?


High risk

Blinding?


High risk



Low risk



High risk


Co-interventions avoided or similar? Unclear risk information not provided



Manchikanti 2001


Participants Private pain management practice in a non-university setting, Paducah, Kentucky.

84 patients with low-back pain with or without lower extremity pain for more than

6 months who did not exhibit neurological deficits and who responded positively to

lidocaine blocks

Interventions (1) Multiple medial branch blocks with a local anesthetic (0.5% lidocaine or 0.25%

bupivacaine) and an equal volume of Sarapin.

(2) Multiple medial branch blocks with a mixture of a local anesthetic (0.5% lidocaine

or 0.25% bupivacaine), an equal volume of Sarapin and 1 mg of methyl prednisolone.



Manchikanti 2001 (Continued)

The injections were given throughout the entire follow-up period

Outcomes Timing of outcomes: before the first injection and at different follow-up moments

throughout a 2.5 years period.

Both groups in improved in pain relief, overall health status, physical, functional and

psychological status and return to work over 2.5 years follow-up. No significant differ-

ences were reported between the groups

Notes Side effects: no complications were reported in any of the patients

Risk of bias


Adequate sequence generation? Unclear risk Randomization procedure not described.


Blinding?


High risk

Blinding?


High risk

Blinding?


Unclear risk unclear in text



Low risk



High risk




Timing outcome assessments similar? High risk



Marks 1992

Methods RCT; Random number system, concealment of assigned technique from referring clin-

icians and patients

Participants Pain or back clinic, Dundee, Scotland.

86 patients with lumbar or lumbosacral pain present most of the time for at least 6

months. Exclusion criteria were a radicular pattern in either lower limb, straight leg

raising limited at less than 60 degrees and no evidence of any progressive spinal disorder

of non-degenerative origin

Interventions (1) Facet joint injection with 0.5 ml DepoMedrol (20 mg methylprednisolone acetate)

followed by 1.5 ml lignocaine. (1%) at the lumbosacral level and at every other level 0.

5 ml DepoMedrol followed by 1.0 ml lignocaine.

(2) Facet nerve block of the medial articular branch of the posterior primary ramus from

L1 to L5

Outcomes Timing of outcomes: before and 30-60 minutes, 1 month and 3 months after infiltration.

The facet joints injections did slightly better in relieving pain than the facet nerve blocks.

This difference reached statistical significance only at 1 month but not immediately after

infiltration, at 2 weeks and at 3 months

Notes Side effects: no serious complications. Transient symptoms, such as headache, paresthesia

of one leg, nausea and worsening of pain occurred 15 times in the injection group and

18 times in the nerve block group

Risk of bias


Adequate sequence generation? Low risk Random number system

Allocation concealment? Low risk A - Adequate - concealment of assigned

technique from referring clinicians and pa-

tients

Blinding?


Low risk

Blinding?



Blinding?


Low risk



Low risk



High risk



Marks 1992 (Continued)





Mauro 2000


Participants Outpatient clinic of the department of Orthopedics of Palermo University Hospital,

Palermo, Italy

60 patients with lumbago or sciatic neuritis of mechanical origin without need for surgical

procedures. They had to present with a proven medical history for low-back pain (lasting

from 6 months to 5 years) and a pain intensity of at least 60 mm as evaluated on a visual

analogue scale

Interventions Intramuscular injections once daily for a 2 week period.

(1) 2 ml ampoules containing 1000 mg Vitamin B12 (Tricortin 1000).

(2) 2 ml placebo ampoules.

Outcomes Timing of outcomes: before and 2 weeks after randomization.

At the end of the treatment period there was a statistically significant difference in im-

provement in pain (visual analogue scale) and disability (Roland Disability Question-

naire) in favor of the Vitamin B12 group

Notes Consumption of paracetamol proved significantly higher in the placebo group compared

to the active treatment group. Side effects: No changes in vital signs, or adverse effects

were noted

Risk of bias


Adequate sequence generation? Unclear risk Randomization procedure not described.


Blinding?



Blinding?





Mauro 2000 (Continued)

Blinding?


Low risk



High risk



High risk





Mayer 2004

Methods RCT; Assignment based on date of the month of their initial visit alternating with patients

allocated to the other group

Participants Department of Orthopedic Surgery, University of Texas, Southwestern Medical Center,

Dallas, Texas.

70 patients with chronic disabling work-related lumbar spine disorders who had lumbar

rigidity between 1 and 3 levels. The mean length of disability varied from 12 (intervention

group) to 16 months (control group)

Interventions (1) Facet joint injection on one to three levels bilaterally. Each point was injected with a

mixture of 1 ml 2% lidocaine, 1 ml 0.5% bupivacaine and 1 ml of a depot corticosteroid

preparation. In addition, a home stretching exercise program was instructed which was

supervised by physiotherapists on each subsequent visit of the patient (on average twice

a week).

(2) Patients in the control group only received the home stretching exercise program

Outcomes Timing of outcomes: before and post-treatment.

No significant differences were found in pain and disability between the groups. The

group which combined injections with home exercises had a significantly greater im-

provement in range of motion at 5 to 7 weeks compared to the control group

Notes Side effects were not reported by the study authors.

Risk of bias




Mayer 2004 (Continued)

Adequate sequence generation? High risk Assignment based on date of the month of

their initial visit alternating with patients

allocated to the other group


Blinding?


High risk

Blinding?


High risk

Blinding?


Low risk



Low risk





Co-interventions avoided or similar? Unclear risk unclear in text


Timing outcome assessments similar? Unclear risk unclear in text

Revel 1999


Participants Department of Rheumatology and Rehabilitation, Hospital Rochin, Paris, France.

80 patients with low-back pain for more than 3 months and with pain graded higher

than 30 mm on a 100 mm visual analogue scale

Interventions Facet joint injections (four or six on both sides or two or three on the same side) consisting

of:

(1) 1 ml 2% lidocaine.

(2) 1 ml saline.

The injections in both groups were followed by an injection of 2 mg cortivazol near the

joint

Outcomes Timing of outcomes: before the first injection and half an hour after the last injection.

Lidocaine provided significantly greater back pain relief than saline



Revel 1999 (Continued)

Notes The study was set up from a diagnostic perspective in order to determine clinical criteria

that could be used to identify patients with painful facet joints. Side effects were not

reported by the study authors

Risk of bias




Blinding?


Low risk

Blinding?


Low risk

Blinding?


Low risk



Low risk



Low risk





Rocco 1989

Methods RCT; randomization procedure not described.

Participants Pain Treatment Service, Brigham and Women’s hospital Boston.

22 patients who had undergone at least one prior laminectomy and who were still

symptomatic. The duration of pain at study entry was not specified

Interventions Epidural injections which were given at 1 month interval for 3 months:

(1) 1.9 ml (75 mg) triamcinolone diacetate plus 1 ml (50 mg) lidocaine.

(2) 8 ml (8 mg) morphine plus 1 ml (50 mg) lidocaine.

(3) 1.9 ml (75 mg) triamcinolone diacetate plus 8 ml (8 mg) morphine plus 1 ml (50



Rocco 1989 (Continued)

mg) lidocaine

Outcomes Timing of outcomes: before randomization, 1 month after randomization and 3 months

after the last injection (6 months after randomization).

No significant differences were reported with regard to pain relief at 1 and 6 months as

measured with a verbal ordinal scale and a visual analogue scale

Notes Side effects: more urinary retention was noted in the triamcinolone plus morphine group.

Nausea, vomiting and pruritis were noted more frequently in the patients given morphine

or triamcolone combined with morphine than in those given triamcolone alone

Risk of bias


Adequate sequence generation? Unclear risk randomization procedure not described.


Blinding?


Low risk

Blinding?


High risk

Blinding?


Low risk



Low risk



Low risk







Serrao 1992


Participants York Pain Clinic, Department of Anaesthetics, York District Hospital, York, UK.

28 patients with mechanical low-back pain were included. The duration of pain ranged

from 1 to 35 years. Exclusion criteria were disc lesions and spinal claudication

Interventions Epidural injections:

(1) 80 mg prednisolone suspended in 10 mL saline (epidural) and 3 mL (5%) dextrose

solution (intrathecal).

(2) 10 mL normal saline (epidural) and 2 mg midazolam dissolved in 3 mL (5%) dextrose

(intrathecal)

Outcomes Timing of outcomes: before and 2 weeks and 2 months after treatment.

No significant differences were reported with regard to pain relief (short form McGill

questionnaire and verbal rating scale) and general improvement at 2 week and 2 months

after treatment

Notes Side effects: Some patients reported headaches (midazolam (N = 7), steroid (N = 8)) or

nausea (midazolam (N = 1), steroid (N = 2))

Risk of bias




Blinding?


Low risk

Blinding?



Blinding?


Low risk



Unclear risk data not provided



Unclear risk data not provided






Serrao 1992 (Continued)


Sonne 1985

Methods RCT; randomization procedure not described.

Participants Department of Rheumatology, Bispebjerg Hospital, Copenhagen, Denmark.

30 patients with low-back pain of longer than 1 month duration with the exception of

patients with herniated disc lesions, osteoporosis, arachnoiditis or ankylosing spondylitis

Interventions Local injections at the site of the iliolumbar ligament with a maximum of three injections

give at one week intervals.

(1) 5 mL lignocaine 1% mixed with 1 mL methylprednisolone.

(2) 5 mL isotonic saline.

Outcomes Timing of outcomes: before the study and at each visit and 2 weeks after completing the

study.

No significant differences between the groups in pain (visual analogue scale) and spinal

flexion at each visit and 2 weeks after completing the study. Self-reported improvement

was assessed 2 weeks after completing the study. 9 out of 15 patients in the methyl-

prednisolone group reported a good or excellent improvement compared to 3 out of 14

patients in the saline group which was a significant difference

Notes Side effects were not reported by the study authors.

Risk of bias


Adequate sequence generation? Unclear risk randomization procedure not described.


Blinding?



Blinding?


High risk

Blinding?


Low risk



Low risk



High risk



Sonne 1985 (Continued)





Takada 2005

Methods Randomized double blind cross-over study; Randomization procedure not described

Participants Department of Anesthesia, Nagasaki Rosai Hospital, Sasebo, Japan.

16 patients diagnosed as having degenerative spinal disease. The length of the history

of low-back pain ranged from 1 to 24 months. Patients who had a severe canal stenosis

with leg paresis or who had received spinal surgery were excluded from the study

Interventions Single epidural injection with:



(3) 8 ml bupivacaine 0.25%.

Test solutions were given in a randomized order at intervals of one week or more

Outcomes Timing of outcome: before and after epidural blockade.

No significant differences in pain scores (visual analogue scale) after epidural blockade

were found

Notes Side effects: one subject in the 0.375% ropivacaine trial was catheterized because of

bladder distension

Risk of bias


Adequate sequence generation? High risk Randomization procedure not described


Blinding?


Low risk

Blinding?


Low risk

Blinding?


Low risk



Takada 2005 (Continued)



Unclear risk data not given



Unclear risk data not given





Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Bonetti 2005 Study population consisted of patients with radiculopathy

Bush 1991 Study was about corticosteroid injections for radiculopathy versus placebo

Cuckler 1985 Study was about corticosteroid injections for radiculopathy versus placebo

Dallas 1987 The drugs were administered by means of a catheter and not directly by means of an injection

Fredman 1999 The drugs were administered by means of a catheter and not directly by means of an injection

Glynn 1988 The drugs were administered by means of a catheter and not directly by means of an injection

Hameroff 1981 Patients who had cervical symptoms were also included and no separate results for the lower back were presented

Mathews 1987 Study was about corticosteroid injections for radiculopathy versus placebo

Ney 2006 Study appeared not to be a RCT

Ofluoglu 2007 Study population consisted of patients with osteoporosis

Oh 2004 Radiofrequency denervation was compared with an injection of a small amount of lidocaine which was considered

a sham treatment

Ongley 1987 Study was about the effectiveness of prolotherapy



(Continued)

Pneumaticos 2006 Two different injection sites were compared and no comparison was made with regard to the type of injection

therapy

Rogers 1992 Study dealt with corticosteroid injections for radiculopathy versus placebo

Simmons 1992 Study was about the effectiveness of intradiscal injections

Stojanovic 2005 Two different needling techniques were compared and no comparison was made with regard to the type of

injection therapy

Tuzun 2003 Study population consisted of acute low-back pain patients



D A T A A N D A N A L Y S E S

Comparison 1. epidural corticosteroids versus placebo injections

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Percentage improved over 1 to 3

months

1 Risk Ratio (M-H, Fixed, 95% CI) Totals not selected

2 Percentage pain relief over 3 to 5

weeks


Comparison 2. epidural corticosteroid injections versus other treatments


studies

No. of


1 General improvement at 2

months


Comparison 3. Facet joint injections with corticosteroids versus placebo injections


studies

No. of


1 Self-rated improvement at 1

month


2 Self rated improvement at 6

months


Comparison 4. Facet joint injections with corticosteroids versus other injections


studies

No. of


1 Improvement in pain severity at

1 month


2 Improvement in pain severity at

3 months




Comparison 5. Facet joint injections with local anaesthetics versus other injections


studies

No. of


1 Pain reduction post-treatment

in positive group (VAS) (facet

joint assumed to be the primary

source of pain)

1 Mean Difference (IV, Fixed, 95% CI) Totals not selected

Comparison 6. Local injections with corticosteroids versus placebo injections


studies

No. of


1 Self-reported improvement at 2

weeks


2 Self-reported improvement

posttreatment


Comparison 7. Local injections with anaesthetics versus placebo injections


studies

No. of


1 Pain intensity at 2 weeks (VAS) 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected

2 Self-reported improvement at 2

weeks


Analysis 1.1. Comparison 1 epidural corticosteroids versus placebo injections, Outcome 1 Percentage

improved over 1 to 3 months.

Review: Injection therapy for subacute and chronic low-back pain

Comparison: 1 epidural corticosteroids versus placebo injections

Outcome: 1 Percentage improved over 1 to 3 months

Study or subgroup corticosteroids Placebo Risk Ratio Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

Beliveau 1971 18/24 16/24 1.13 [ 0.78, 1.62 ]

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours placebo



Analysis 1.2. Comparison 1 epidural corticosteroids versus placebo injections, Outcome 2 Percentage pain

relief over 3 to 5 weeks.


Comparison: 1 epidural corticosteroids versus placebo injections

Outcome: 2 Percentage pain relief over 3 to 5 weeks

Study or subgroup Corticosteroids Placebo Risk Ratio Risk Ratio


Breivik 1976 10/16 13/19 0.91 [ 0.56, 1.49 ]

0.1 0.2 0.5 1 2 5 10

Favours placebo Favours treatment

Analysis 2.1. Comparison 2 epidural corticosteroid injections versus other treatments, Outcome 1 General

improvement at 2 months.


Comparison: 2 epidural corticosteroid injections versus other treatments

Outcome: 1 General improvement at 2 months

Study or subgroup Corticosteroids Midazolam Risk Ratio Risk Ratio


Serrao 1992 5/14 7/14 0.71 [ 0.30, 1.72 ]

0.1 0.2 0.5 1 2 5 10

Favours Midazolam Favours treatment



Analysis 3.1. Comparison 3 Facet joint injections with corticosteroids versus placebo injections, Outcome 1

Self-rated improvement at 1 month.


Comparison: 3 Facet joint injections with corticosteroids versus placebo injections

Outcome: 1 Self-rated improvement at 1 month

Study or subgroup Favours placebo Placebo Risk Ratio Risk Ratio


Carette 1991 20/49 16/48 1.22 [ 0.73, 2.07 ]

0.1 0.2 0.5 1 2 5 10


Analysis 3.2. Comparison 3 Facet joint injections with corticosteroids versus placebo injections, Outcome 2

Self rated improvement at 6 months.


Comparison: 3 Facet joint injections with corticosteroids versus placebo injections

Outcome: 2 Self rated improvement at 6 months

Study or subgroup Favours placebo Placebo Risk Ratio Risk Ratio


Carette 1991 46/48 15/47 3.00 [ 1.97, 4.58 ]

0.1 0.2 0.5 1 2 5 10




Analysis 4.1. Comparison 4 Facet joint injections with corticosteroids versus other injections, Outcome 1

Improvement in pain severity at 1 month.


Comparison: 4 Facet joint injections with corticosteroids versus other injections

Outcome: 1 Improvement in pain severity at 1 month

Study or subgroup Facet injection Facet nerve block Risk Ratio Risk Ratio


Marks 1992 27/42 24/44 1.18 [ 0.83, 1.68 ]

0.1 0.2 0.5 1 2 5 10

Favours facet nerve block Favours treatment

Analysis 4.2. Comparison 4 Facet joint injections with corticosteroids versus other injections, Outcome 2

Improvement in pain severity at 3 months.


Comparison: 4 Facet joint injections with corticosteroids versus other injections

Outcome: 2 Improvement in pain severity at 3 months

Study or subgroup Facet injection Facet nerve block Risk Ratio Risk Ratio


Marks 1992 16/41 12/42 1.37 [ 0.74, 2.52 ]

0.1 0.2 0.5 1 2 5 10

Favours Facet nerve block Favours treatment



Analysis 5.1. Comparison 5 Facet joint injections with local anaesthetics versus other injections, Outcome 1

Pain reduction post-treatment in positive group (VAS) (facet joint assumed to be the primary source of pain).


Comparison: 5 Facet joint injections with local anaesthetics versus other injections

Outcome: 1 Pain reduction post-treatment in positive group (VAS) (facet joint assumed to be the primary source of pain)

Study or subgroup Lidocaine PlaceboMean

DifferenceMean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Revel 1999 42 35.36 (23.6) 38 11.87 (17.44) 23.49 [ 14.45, 32.53 ]

-50 -25 0 25 50


Analysis 6.1. Comparison 6 Local injections with corticosteroids versus placebo injections, Outcome 1 Self-

reported improvement at 2 weeks.


Comparison: 6 Local injections with corticosteroids versus placebo injections

Outcome: 1 Self-reported improvement at 2 weeks



Garvey 1989 4/14 5/13 0.74 [ 0.25, 2.18 ]

0.1 0.2 0.5 1 2 5 10




Analysis 6.2. Comparison 6 Local injections with corticosteroids versus placebo injections, Outcome 2 Self-

reported improvement posttreatment.


Comparison: 6 Local injections with corticosteroids versus placebo injections

Outcome: 2 Self-reported improvement posttreatment



Sonne 1985 9/14 3/15 3.21 [ 1.09, 9.51 ]

0.1 0.2 0.5 1 2 5 10


Analysis 7.1. Comparison 7 Local injections with anaesthetics versus placebo injections, Outcome 1 Pain

intensity at 2 weeks (VAS).


Comparison: 7 Local injections with anaesthetics versus placebo injections

Outcome: 1 Pain intensity at 2 weeks (VAS)

Study or subgroup anaesthetics PlaceboMean

DifferenceMean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Collee 1991 21 30.5 (26.1) 20 43.8 (27.5) -13.30 [ -29.73, 3.13 ]

-50 -25 0 25 50

Favours treatment Favours placebo



Analysis 7.2. Comparison 7 Local injections with anaesthetics versus placebo injections, Outcome 2 Self-

reported improvement at 2 weeks.


Comparison: 7 Local injections with anaesthetics versus placebo injections

Outcome: 2 Self-reported improvement at 2 weeks

Study or subgroup Anaesthetics Placebo Risk Ratio Risk Ratio


Collee 1991 11/21 6/20 1.75 [ 0.80, 3.82 ]

0.1 0.2 0.5 1 2 5 10


A D D I T I O N A L T A B L E S

Table 1. Definitions of internal validity criteria - risks of bias

criteria/definition

Method of randomisation adequate: A random (unpredictable) assignment sequence. Examples of adequate methods are computer

generated random number table and use of sealed opaque envelopes. Methods of allocation using date of birth, date of admission,

hospital numbers, or alternation should not be regarded as appropriate

Concealment of treatment allocation: Assignment generated by an independent person not responsible for determining the eligibility

of the patients; this person has no information about the persons included in the trial and has no influence on the assignment sequence

or on the decision about eligibility of the patient

Blinding of patients: The reviewer determines if there was enough information about the blinding of the care provider to score a yes

Blinding of care providers: The reviewer determines if there was enough information about the blinding of the patient to score a yes

Blinding of outcome assessors: The reviewer determines if there was enough information about the blinding of the outcome assessor

to score a yes

Drop-out rate described and acceptable: The number of participants who were included in the study but did not complete the

observation period or were not included in the analysis must be described and reasons given. If the percentage of drop-outs does not

exceed 20% for short-term follow-up and 30% for long-term follow-up and does not lead to substantial bias, a yes is scored. (N.B.,

these percentages are arbitrary, not supported by literature)

Intention-to-treat analyses: All randomized patients are reported/analyzed in the group to which they were allocated by randomization

for the most important moments of effect measurement (minus missing values) irrespective of non-compliance and co-interventions

Similarity of baseline characteristics: In order to receive a yes, groups have to be similar at baseline regarding demographic factors,

duration and severity of complaints and value of main outcome measure(s)



Table 1. Definitions of internal validity criteria - risks of bias (Continued)

Co-interventions avoided or similar: Co-interventions should either be avoided in the trial design or comparable between the index

and control groups

Compliance acceptable: The reviewer determines if the compliance to the interventions is acceptable, based on the reported intensity,

duration, number, and frequency of sessions for both the index intervention(s) and control intervention(s)

Timing outcome assessments similar: Timing of outcome assessment be identical for all intervention groups and for all important

outcome assessments

Table 2. Clinical Relevance questions

questions

A) Are the patients described in detail so that you can decide whether they are comparable to those that you see in your practice?

B) Are the interventions and treatment settings described well enough so that you can provide the same for your patients?

C) Were all clinically relevant outcomes measured and reported?

D) Is the size of the effect clinically important? We considered a 20 % improvement in pain scores (Salaffi 2004) and a 10%

improvement in functioning outcomes (Bombardier 2000) to be clinically important.

E) Are the likely treatment benefits worth the potential harms?

Table 3. Clinical relevance

reference A B C D E

Aldrete 2003 - + + - -

Beliveau 1971 ? + ? - -

Breivik 1976 + + + + ?

Carette 1991 + + + - -

Collee 1991 + + - - -

Fuchs 2005 + + + - -

Garvey 1989 - + - - -

Lierz 2004 ? + - - -

Lilius 1990 + + + - ?

Manchikanti 2001 - + + - -



Table 3. Clinical relevance (Continued)

Marks 1992 + + - - -

Mauro 2000 + ? + + +

Mayer 2004 + + + - -

Revel 1999 + + - + +

Rocco 1989 - + - - -

Serrao 1992 + + + - -

Sonne 1985 - - + + -

Takada 2005 - + - - ?

A P P E N D I C E S

Appendix 1. Search Strategies

PubMed

Phase1: (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[mh] OR random allo-

cation[mh] OR double-blind method[mh] OR single-blind method[mh] OR clinical trial[pt] OR clinical trials[mh] OR “clinical

trial”[tw]) OR ((single*[tw] OR doubl*[tw] OR trebl*[tw] OR tripl*[tw]) AND (mask*[tw] OR blind*[tw])) OR (“latin square”[tw])

OR placebos[mh] OR placebo*[tw] OR random*[tw] OR research design[mh:noexp] OR comparative study[mh] OR evaluation

studies[mh] OR follow-up studies[mh] OR prospective studies[mh] OR cross-over studies[mh] OR control*[tw] OR prospective*[tw]

OR volunteer*[tw] NOT (animal[mh] NOT human[mh])

Phase 2: (low back pain OR backache[tw] OR Lumbago[tw])

Phase 3: (injections) OR (injection) OR (chemonucleolysis) OR (rhizotomy) OR (facet denervation) OR (thermolesions)

Phase 4: 1 AND 2 AND 3

EMBASE

#1 clinical article

#2 clinical study

#3 clinical trial

#4 controlled study

#5 randomized controlled trial

#6 major clinical study

#7 double blind procedure

#8 multicentre study

#9 single blind procedure

#10 crossover procedure

#11 placebo

#12 (1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11)

#13 allocat$

#14 assign$



#15 blind$

#16 (clinic$ adj25 (study or trial))

#17 compar$

#18 control$

#19 cross?over

#20 factorial$

#21 follow?up

#22 placebo$

#23 prospectiv$

#24 random$

#25 ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$))

#26 trial

#27 (versus or vs)

#28 (13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28)

#29 (12 or 28)

#30 human

#31 nonhuman

#32 animal

#33 animal experiment

#34 (31 or 32 or 33)

#35 (30 and 34)

#36 (29 not 34)

#37 (29 and 35)

#38 (36 or 37)

#39 low back pain

#40 backache

#41 lumbago

#42 (#39 or #40 or #41)

#43 injection

#44 injections

#45 chemonucleolysis

#46 rhizotomy

#47 facet denervation

#48 thermolesion

#49 (#43 or #44 or #45 or #46 or #47 or #48)

#50 (#49 and #42 and #38)

W H A T ’ S N E W

Last assessed as up-to-date: 29 March 2007.

Date Event Description

19 January 2011 Amended Contact details updated.



H I S T O R Y

Protocol first published: Issue 3, 1996

Review first published: Issue 4, 1999

Date Event Description

23 November 2009 Amended Contact details updated.

12 May 2008 Amended converted to new review format

12 May 2008 New citation required but conclusions have not

changed

This review is an update of a previously withdrawn

review. In an attempt to increase clinical homogene-

ity, the withdrawn review was split, and the current

review no longer contains trials on the effects of in-

tradiscal therapy, prolotherapy, or epidural steroids for

radiculopathy due to disc herniation. These are topics

of current or future Cochrane reviews

As before, the review authors concluded that there was

insufficient evidence to support the use of injection

therapy in subacute and chronic low-back pain. How-

ever, it cannot be ruled out that specific subgroups of

patients may respond to a specific type of injection

therapy

12 May 2008 New search has been performed The search was updated and eight new RCTs were

included for the scope of the current review.

In the current review, the internal validity of the RCTs

was measured using the eleven criteria outlined in the

2003 Updated Cochrane Back Review Group method

guidelines. Half of the RCTs were rated as having a

low risk of bias

25 January 2006 New citation required but conclusions have not

changed

Review was withdrawn from publication because it was

out of date

C O N T R I B U T I O N S O F A U T H O R S

Bart Staal and Rob de Bie updated the searches for new trials, conducted the study selection, quality assessment, data extraction and

analysis of all new studies. Patty Nelemans and Rob de Bie conducted the study selection, quality assessment, data extraction and analysis

of all studies included in the original review. Bart Staal drafted the present manuscript. All authors critically revised and approved the

manuscript.



D E C L A R A T I O N S O F I N T E R E S T

None declared

I N D E X T E R M SMedical Subject Headings (MeSH)

Anesthesia, Conduction; Anesthetics [∗administration & dosage]; Anti-Inflammatory Agents [∗administration & dosage]; Chronic

Disease; Glucocorticoids [∗administration & dosage]; Injections, Intra-Articular; Injections, Spinal [∗methods]; Low Back Pain [∗drug

therapy]; Randomized Controlled Trials as Topic; Steroids

MeSH check words

Humans



cochrane database of systematic reviews (reviews) || injection therapy for subacute and chronic...

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